PMID: 

Colloids Surf B Biointerfaces. 2019 Oct 23 ;186:110603. Epub 2019 Oct 23. PMID: 31846892

Abstract Title: 

Improved chemotherapeutic efficacy against resistant human breast cancer cells with co-delivery of Docetaxel and Thymoquinone by Chitosan grafted lipid nanocapsules: Formulation optimization, in vitro and in vivo studies.

Abstract: 

In recent years, multi-targeted chemotherapeutic combinations have received considerable attention in solid tumor chemotherapy. Here, we optimized low-molecular-weight chitosan (CS)-grafted lipid nanocapsules (LNCs, referred to as CLNCs) for the co-delivery of docetaxel (DTX) and thymoquinone (THQ) to treat drug-resistant breast cancer. We first screened size reduction techniques (homogenization vs ultrasonication), and then the 3-Box-Behnken design was employed to determine optimal conditions of the final LNCs with the desired quality attributes. Uncoated LNCs had a particle size of 141.7 ± 2.8 nm (Polydispersity index, PdI: 0.17 ± 0.02) with entrapment efficiency (%EE) of 66.1 ± 3.5 % and 85.3 ± 3.1 % for DTX and THQ, respectively. The CS functionalization of LNCs improved the uptake and endosomal escape effect, and led to a significantly higher cytotoxicity against MCF-7 and triple-negative (MDA-MB-231) breast cancer cells. Furthermore, an enhanced antiangiogenic effect was observed with DTX- and THQ-carrying CLNCs in the Chick embryo chorioallantoic membrane (CAM) assay.

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PMID: 

J Food Biochem. 2019 Dec 26:e13131. Epub 2019 Dec 26. PMID: 31876968

Abstract Title: 

Pharmacological studies on the efficacy of a thymoquinone-containing novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in rats.

Abstract: 

The aim of this study was to investigate the protective effect of a novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in six groups of rats. Group I: Normal control; Group II: cisplatin (5 mg/kg i.p.); Group III: cisplatin (5 mg/kg i.p.) + cystone (750 mg/kg p.o.); Group IV: cisplatin + Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone (CFCT) (25 mg/kg p.o.); Group V: cisplatin + CFCT-50; Group VI: cisplatin + CFCT-100. The rats were treated for 4 weeks. Serum and tissue biochemical parameters were assessed. The results showed that aspartate aminotransferase (131.8 IU/L), alanine aminotransferase (66.75 IU/L), alkaline phosphatase (168.67 IU/L), cholesterol (135.15 IU/L), serum urea (56.76 mg/dl), blood urea nitrogen (47.52 mg/dl), and creatinine (3.11 mg/dl) were significantly elevated (p 

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PMID: 

Life Sci. 2020 Jan 14:117299. Epub 2020 Jan 14. PMID: 31953157

Abstract Title: 

Thymoquinone and pentoxifylline enhance the chemotherapeutic effect of cisplatin by targeting Notch signaling pathway in mice.

Abstract: 

AIMS: Notch signaling is highly implicated in several cancers and chemoresistance. Therefore, Notch-targeted therapies might be beneficial in enhancing chemotherapeutic effect and cancer regression. This study aimed to investigate implication of Notch in development and progression of solid Ehrlich carcinoma (SEC) and enhancement of anticancer effect of cisplatin (CIS) by addition of thymoquinone (TQ) and pentoxifylline (PTX) through modulation of Notch.MAIN METHODS: SEC was induced in mice as model for mammary carcinoma by s.c. injection of 1 × 10Ehrlich cells into back of the mice. On 12th day, solid tumor was developed and mice were divided into seven groups; tumor control, early CIS (ECIS), ECIS + ETQ, ECIS + ETQ + EPTX, late CIS (LCIS), LCIS + LTQ, and LCIS + LTQ + LPTX. Early treatment was started on 12th day, whereas late treatment was begun on 19th day from tumor inoculation. At the endpoint, samples were collected for detection of Notch1, Hes1, Jagged1, β-catenin, TNF-α, IL-6, IFN-γ, IL-2, VEGF, apoptosis, CD4, and CD8.KEY FINDINGS: Adding PTX and TQ to CIS significantly reduced Notch1, Hes1, Jagged1,β-catenin, TNF-α, IL-6, IFN-γ, and VEGF with increment in IL-2, CD4, CD8, and apoptotic cells. Moreover, early treated groups showed remarkable attenuation in tumor growth and the relevant parameters compared to their counterpart later groups.SIGNIFICANCE: Addition of PTX with TQ to CIS showed a synergistic chemotherapeutic action and induced better oncostatic effect mainly through Notch suppression. Consequently, shutting Notch could be of great interest in promoting chemosensetivity and cancer control.

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PMID: 

Metabolites. 2020 Jan 7 ;10(1). Epub 2020 Jan 7. PMID: 31936061

Abstract Title: 

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI.

Abstract: 

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

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PMID: 

J Basic Clin Physiol Pharmacol. 2020 Jan 11. Epub 2020 Jan 11. PMID: 31926081

Abstract Title: 

Increased blood lead level induces oxidative stress and alters the antioxidant status of spray painters.

Abstract: 

Background The aim of this study was to know the present scenario of blood lead level and its effect on serum lipid peroxide and antioxidant parameters of spray painters. Methods We included 42 male spray painters and 50 control subjects with an age range of 20-45 years. Blood lead level, serum lipid peroxide and antioxidant parameters, i.e. erythrocyte catalase, superoxide dismutase (SOD), plasma ceruloplasmin, nitric oxide, uric acid and bilirubin, were quantified by standard methods. Results We observed the significant elevated blood lead (p

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PMID: 

Reprod Biol Endocrinol. 2020 Jan 11 ;18(1):2. Epub 2020 Jan 11. PMID: 31926565

Abstract Title: 

Attenuation of sleep deprivation dependent deterioration in male fertility parameters by vitamin C.

Abstract: 

PURPOSE: Male fertility is multifaceted and its integrity is as well multifactorial. Normal spermatogenesis is dependent on competent testicular function; namely normal anatomy, histology, physiology and hormonal regulation. Lifestyle stressors, including sleep interruption and even deprivation, have been shown to seriously impact male fertility. We studied here both the effects and the possible underlying mechanisms of vitamin C on male fertility in sleep deprived rats.METHODS: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (remained in their cages with free access to food and water), sleep deprivation (SD) group (subjected to paradoxical sleep deprivation for 5 consequent days, rats received intra-peritoneal injections of vehicle daily throughout the sleep deprivation), and sleep deprivation vitamin C-treated (SDC) group (subjected to sleep deprivation for 5 consequent days with concomitant intra-peritoneal injections of 100 mg/kg/day vitamin C). Sperm analysis, hormonal assay, and measurement of serum oxidative stress and inflammatory markers were performed. Testicular gene expression of Nrf2 and NF-κβ was assessed. Structural changes were evaluated by testicular histopathology, while PCNA immunostaining was conducted to assess spermatogenesis.RESULTS: Sleep deprivation had significantly altered sperm motility, viability, morphology and count. Serum levels of cortisol, corticosterone, IL-6, IL-17, MDA were increased, while testosterone and TAC levels were decreased. Testicular gene expression of Nrf2 was decreased, while NF-κβ was increased. Sleep deprivation caused structural changes in the testes, and PCNA immunostaining showed defective spermatogenesis. Administration of vitamin C significantly countered sleep deprivation induced deterioration in male fertility parameters.CONCLUSION: Treatment with vitamin C enhanced booth testicular structure and function in sleep deprived rats. Vitamin C could be a potential fertility enhancer against lifestyle stressors.

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PMID: 

Food Res Int. 2020 Feb ;128:108749. Epub 2019 Nov 7. PMID: 31955788

Abstract Title: 

The role of nutraceuticals in prevention and treatment of hypertension: An updated review of the literature.

Abstract: 

Hypertension (HTN) is a worldwide epidemic in both developed and developing countries. It is one of the leading causes of major health problems such as cardiovascular disease, stroke, and heart attack. In recent years, several studies have reported associations between specific dietary ingredients and improving HTN. Nutraceuticals are natural food components with pharmacological properties. Reports suggest that functional foods and nutraceutical ingredients might support patients to obtain the desired therapeutic blood pressure (BP) goals and reduce cardiovascular risks by modulating various risk factors such as oxidative stress, renin-angiotensin system hyperactivity, inflammation, hyperlipidemia, and vascular resistance. We review the recent clinical experiments that have evaluated the biological and pharmacological activities of several types of nutraceuticals, including sour tea, cocoa, common spices, vitamin C, vitamin E, lycopene, flavonoids, coenzyme Q10, milk's tripeptides, calcium, magnesium, polyunsaturated fatty acids, and prebiotics in preventing and treating HTN. This review summarizes recent knowledge about the impact of common nutraceuticals for the regulation of BP.

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PMID: 

Environ Sci Technol. 2020 Jan 21. Epub 2020 Jan 21. PMID: 31961142

Abstract Title: 

Lung anti-oxidant depletion: a predictive indicator of cellular stress induced by ambient fine particles.

Abstract: 

Regulations on ambient particulate matter (PM) are becoming more stringent due to adverse health effects arising from PM exposure. PM-induced oxidant production is a key mechanism behind the observed health effects and is heavily dependent on PM composition. Measurement of the intrinsic oxidative potential (OP) of PM could provide an integrated indicator of PM bioreactivity, and could serve as a better metric of PM hazard exposure than PM mass concentration. The OP of two chemically-contrasted PM2.5 samples was compared through four acellular assays and OP predictive capability was evaluated in different cellular assays on two in vitro lung cell models. PM2.5 collected in Paris at site close to the traffic exhibited a systematically higher OP in all assays compared to PM2.5 enriched in particles from domestic wood burning. Similar results were obtained for oxidative stress, expression of anti-oxidant enzymes and pro-inflammatory chemokine in human bronchial epithelial and endothelial cells. The strongest correlations between OP assays and cellular responses were observed with the antioxidant (ascorbic acid and glutathione) depletion (OPAO) assay. Multivariate regression analysis from OP daily measurements suggested that OPAO was strongly correlated with PAH at traffic site while it was correlated with potassium for the domestic wood burning sample.

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PMID: 

Pak J Biol Sci. 2020 Jan ;23(2):126-131. PMID: 31944071

Abstract Title: 

Potency of Papaya Leaf (Carica papayaL.) as Toxicant and Repellent against German Cockroach (Blattella germanicaL.).

Abstract: 

BACKGROUND AND OBJECTIVE: Papaya leaves have the potency to be developed as alternative insecticide to control the German cockroaches that have been resistant to synthetic insecticides. This study aimed to determine the potency of ethanolic extract of papaya leaf as toxicant and repellent against 2 populations of German cockroaches which are known resistant to synthetic insecticide.MATERIALS AND METHODS: The methods that used was contact toxicity test and repellency test. The ethanolic extract of papaya leaf residues were used in contact toxicity test of 4 residues and a sub-lethal residue in repellency test. Three populations of German cockroach were collected in field and kept in laboratory.RESULTS: Lethal residue 50% (LR50) of ethanolic extract of papaya leaf between 2.97-4.72 mg cm-2 while lethal residue 90% (LR90) between 6.05-8.92 mg cm-2 and very effective killed all population of German cockroach. Repellency value of ethanolic extract of papaya leaf with a sub-lethal residue of 0.39 mg cm-2 between 88.89 -94.74% and level of repellency was very repellent.CONCLUSION: Ethanolic extract of papaya leaf could be formulated as a potent natural insecticide to control populations of German cockroach that have been resistant to synthetic insecticides.

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PMID: 

Int Immunopharmacol. 2019 Dec ;77:105980. Epub 2019 Nov 4. PMID: 31699670

Abstract Title: 

Ferulic acid attenuates oxidative DNA damage and inflammatory responses in microglia induced by benzo(a)pyrene.

Abstract: 

Over-activation of microglia disrupts the physiological homeostasis of the brain, and induces inflammatory response and other processes which are implicated in neurodegenerative diseases. Therefore, theoretically, suppression of neuroinflammation would slow the progression of neurodegenerative disease. In this study, we investigated the possible protective effects of Ferulic acid (FA) against benzo(a)pyrene (BaP)-induced microglial activation using BV2 cells as the model system. Exposure of BV2 cells to BaP (10 μM) significantly increased DNA damage and the production of pro-inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), malondialdehyde (MDA), and cytokines (interleukins-1β and -6). On the other hand, when BaP-treated BV2 cells were further incubated with FA (10, 20, 40, or 80 mg/mL) for another 24 h, a significant reduction in BaP-induced DNA damage and the release of multiple pro-inflammatory and cytotoxic factors (including interleukin-1β, interleukin-6, NO, and ROS) was observed in a dose-dependent manner. Further study revealed that the microglial NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) signaling pathway was involved in the protective effect of FA. Taken together, these results suggested that FA suppressed BaP-induced toxicity in microglia, and thus mayexert neuroprotective effects by inhibiting microglia-mediated pro-inflammatory response.

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